OFFICE OF CHEMICAL 

SAFETY AND POLLUTION 

PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

 

 PC Code: 121027 

DP Barcodes: 412827

 Date: May 6, 2014 

MEMORANDUM 

SUBJECT: Environmental Fate and Ecological Risk Assessment for Proposed Use of 

Methoxyfenozide on Pineapple. 

TO: Olga Odiott, Risk Manager 

Mark Suarez, Product Manager 

Insecticide Branch 

Registration Division (Mail Code 7505P) 

 

FROM: Mary Clock-Rust, Biologist 

 Karen Milians, Ph.D., Chemist 

Ideliz Negrón-Encarnación, Ph.D., Chemist 

 Environmental Risk Branch IV 

 Environmental Fate and Effects Division (7507P) 

REVIEWED 

BY: Thomas Steeger, Ph.D., Senior Science Advisor 

Jim Carleton, Ph.D., Environmental Scientist 

 Environmental Risk Branch IV 

Environmental Fate and Effects Division (7507P)

APPROVED 

BY: Sarah Winfield, Acting Branch Chief 

 Environmental Risk Branch IV 

 Environmental Fate and Effects Division (7507P) 

The Environmental Fate and Effects Division (EFED) has completed a review of the proposed use 

of the insecticide methoxyfenozide [Intrepid® 2F, EPA Reg. No. 62719-442 (22.6 % active 

ingredient)] on pineapple. 

Conclusions on the Proposed Use on Pineapple 

EFED’s analysis determined that there is potential for direct adverse effects to Federally listed 

threatened and endangered species (hereafter referred to as “listed”) species of freshwater aquatic 

invertebrates from the proposed use of methoxyfenozide on pineapple. Specifically, the proposed 

use has the potential for direct effects to listed freshwater invertebrates following acute exposure 
-Page 2 of 36- 

and direct effects to listed and non-listed freshwater invertebrate species following chronic 

exposure. The likelihood of direct adverse effects to birds, mammals, fish, and terrestrial and 

aquatic plants and estuarine/marine invertebrates from exposure to methoxyfenozide as a result of 

the proposed use on pineapples is expected to be low. However, the extent to which other taxa that 

may depend on freshwater aquatic invertebrate species may be indirectly affected is uncertain. The 

potential for direct adverse effects to adult honey bees (Apis mellifera) is considered low as a 

preliminary review of recently submitted data do not indicate that honey bee brood (larvae/pupae) 

are adversely affected by exposure to the compound. Because of methoxyfenozide’s mode of 

action as an ecdysone agonist, there is uncertainty as to the extent to which larval stages of other 

insects (excluding honey bees) may be affected since the compound is intended to induce 

premature molts thereby resulting in the death of the target organism. 

Methoxyfenozide is persistent and moderately mobile (Table 2), which, combined with the fact 

that this compound acts through pathways which are common to a broad range of organisms which 

rely on the molting hormone ecdysone, makes it plausible that methoxyfenozide may pose greater 

long-term ecological risk than what is suggested by this screening-level assessment. No data are 

available to assess the potential risks of methoxyfenozide exposure to terrestrial plants or to aquatic 

vascular plants; however, given the mode of action of methoxyfenozide as an insect growth 

regulator, there is uncertainty whether the compound would have any effects on plants. The data 

available for aquatic non-vascular plants did not indicate any adverse effects from exposure up to 

the solubility limit of the compound (3.3 mg/L). Further, no reports of plant damage resulting from 

exposure to methoxyfenozide have been recorded in EFED’s incident databases. 

EFED notes that the maximum application rate and the annual application rate may be misstated 

on Intrepid® labels. The maximum single application rate is stated as 7 fl oz/A (label states this as 

0.10 lb a.i./A) and the maximum annual application rate is stated as 28 fl oz/A (label states 0.44 lb 

a.i./A). At 2 lb a.i./gal, that is 0.015 lb a.i./fl oz or 0.109375 lb a.i./7 oz. Based on these 

calculations, EFED used 0.11 lb a.i./A as the maximum single application rate to assess potential 

risk. 

Ecological Effects Data 

Methoxyfenozide is very highly toxic to freshwater invertebrates and moderately toxic to other 

aquatic organisms on an acute exposure basis. Methoxyfenozide is practically non-toxic to the 

Northern bobwhite quail (Colinus virginianus), rat, and adult honey bees (Apis mellifera). More 

recently submitted data are under review since the last risk assessment action for methoxyfenozide 

(USEPA, 2013). The studies are summarized below. There are no outstanding data gaps for 

ecological effects data for which data have not been submitted. 

The registrant has submitted data (MRID 489387-01) examining the effects of methoxyfenozide 

on the development of amphibians, using the African clawed frogs (Xenopus laevis), in response 

to uncertainties regarding potential impacts on the hypothalamic-pituitary-thyroid axis (HPT). 

This amphibian study is currently under review in EFED. 

Also, the registrant has submitted additional studies (MRIDs 489622-01, 489622-02, 489622-03) 

on honey bee larvae/pupae (brood) and on methoxyfenozide residues in bee colonies from almonds 

treated with methoxyfenozide. These studies were submitted to address uncertainty regarding the 
-Page 3 of 36- 

potential of methoxyfenozide to affect honey bee molting. While EFED has not yet completed the 

review process for these studies, preliminary results indicate that methoxyfenozide does not result 

in adverse effects to honey bee larvae and pupae development, nor does it affect colony 

overwintering survival, although uncertainties have been identified in these studies. 

Finally, the registrant submitted data on red swamp crayfish (Procambarus clarkia) to address 

uncertainty whether other aquatic organisms that molt may be sensitive to methoxyfenozide. In 

this study, exposure of crayfish to methoxyfenozide did not affect survival, growth (length or 

weight), total number of molts or number of molts per females in crayfish (EC50: >190 μg a.i./L; 

NOAEC: 190 μg a.i./L; MRID 457027-02). The study is scientifically sound and classified as 

supplemental because it is a non-guideline study (MRID 457027-02). 

The Ecological Incident Information System (EIIS) database contains five incidents for 

methoxyfenozide. All five incidents reported bee kills in which methoxyfenozide was mentioned. 

Four reported incidents took place in California, and one in New York State. For all of these 

incidents, more than one pesticide was named along with methoxyfenozide. Since 

methoxyfenozide alone is not acutely toxic to adult bees on an acute contact or oral exposure basis 

and since these beekill incidents involved the loss of adult bees, it is uncertain that 

methoxyfenozide was the cause of these losses. EPA does not have toxicity data nor does it 

conduct risk assessments for tank mixes of different chemicals or combinations of active 

ingredients. It is therefore unknown whether the toxicity of methoxyfenozide to bees is enhanced 

or otherwise affected by other chemicals that may be tank mixed with it or sprayed concurrently. 

Environmental Fate Data

One of the outstanding data requirements for methoxyfenozide was identified in the initial 

Section 3 registration (i.e., Three years after use, obtaining approval for and conducting 

monitoring of surface water and sediment in a representative sample of high use areas in 

proximity to surface water). 

The main purpose of this data requirement was to address EPA’s concern that multiple years of 

Intrepid® use may result in accumulation of methoxyfenozide residues in water and/or sediment. 

DAS (Dow Agricultural Science) submitted an interim report regarding a monitoring study on lotic 

(flowing) (e.g. rivers) and lentic water bodies (e.g. ponds) and associated benthic sediment being 

conducted in each of the following states: California, Mississippi, and Michigan. More details 

about the report are provided in subsequent sections. The final monitoring report was submitted 

by DAS on April 18, 2014 and it is currently under review. 
-Page 4 of 36- 

OFFICE OF CHEMICAL 

SAFETY AND 

POLLUTION 

PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

Environmental Fate and Ecological Risk Assessment for 

the Proposed Use of Methoxyfenozide on Pineapple. 

Methoxyfenozide 

CAS Registry No: 161050-58-4 PC Code: 121027 

Prepared by:

Mary Clock-Rust, Biologist 

Karen Milians, Ph.D., Chemist 

Ideliz Negrón-Encarnación, Ph.D., Chemist 

U.S. Environmental Protection Agency 

Office of Pesticide Programs 

Environmental Fate and Effects Division 

Environmental Risk Branch IV 

1200 Pennsylvania Ave., NW 

Mail Code 7507P 

Washington, DC 20460

Reviewed by:

Sarah Winfield, Acting Branch Chief 

Thomas Steeger, Ph.D., Senior Science Advisor 

Jim Carleton, Ph.D., Senior Scientist 

May 6, 2014
5

Executive Summary 

Methoxyfenozide is a registered insecticide (insect growth regulator) for a variety of agricultural 

as well as non-agricultural uses. The chemical acts as an ecdysone agonist that induces a 

precocious incomplete molt in invertebrates, particularly lepidopterans. After ingestion of toxic 

doses, sensitive larvae stop feeding and the molting process initiates prematurely leading to 

desiccation and ultimately, death. 

Methoxyfenozide is proposed for use to control lepidopterous larvae pests in pineapple in Hawaii. 

Intrepid® would be applied as a foliar spray at a rate of 4 to 7 fl. oz/Acre or 0.06 to 0.10 lb a.i./acre, 

with a minimum retreatment interval of 7 days. The proposed yearly maximum application rate is 

0.44 lb a.i./acre/year. 

Methoxyfenozide is persistent and moderately mobile; once introduced into the environment, 

methoxyfenozide could travel to key aquatic environmental compartments and persist for extended 

periods of time, impacting a broad range of aquatic species particularly in sandy soils where 

surface and groundwater can be confluent. 

Based on the maximum application rate for the proposed use, there is potential for direct adverse 

effects to Federally-listed threatened/endangered (hereafter referred to as “listed”) freshwater 

aquatic invertebrates. 

EFED’s analysis determined that the proposed use has the potential for direct effects to listed 

freshwater invertebrates following acute exposure and to listed and non-listed freshwater 

invertebrates following chronic exposure. The likelihood of direct adverse effects to birds, 

mammals, fish, and terrestrial and aquatic plants and estuarine/marine invertebrates from exposure 

to methoxyfenozide as a result of the proposed use on pineapples is expected to be low. However, 

the extent to which other taxa that may depend on freshwater aquatic invertebrate species may be 

indirectly affected is uncertain. The potential for direct adverse effects to adult honey bees is 

considered low and a preliminary review of recently submitted data do not indicate that honey bee 

brood (larvae/pupae) are adversely affected by exposure to the compound. Because of 

methoxyfenozide’s mode of action as an ecdysone agonist, there is uncertainty as to the extent to 

which larval stages of other insects may be affected since the compound is intended to induce 

premature molts thereby resulting in the death. 

Introduction 

This assessment evaluates potential risks to non-target species resulting from the proposed new 

uses of Intrepid® 2F insecticide (22.6 % active ingredient) on pineapple. This use has been 

proposed by the technical registrant, Dow AgroSciences (DAS). 

In 2013, EFED completed an ecological risk assessment (USEPA 2004) for methoxyfenozide on 

a variety of uses, including herb subgroup 19A (except chives), dates, sorghum, fruiting vegetable 

group 8-10, pome fruit group 11-10, berry subgroups 13-07 A, F & G, and tropical tree fruits 

(sugar apple, cherimoya, atemoya, custard apple, ilama, soursop, and biriba) (USEPA, 2013). 
6

Recently, EFED completed the preliminary problem formulation for the environmental fate, 

ecological risk, endangered species, and drinking water exposure assessments to be conducted as 

part of the Registration Review of methoxyfenozide (USEPA, 2013b). 

Mode of Action 

Methoxyfenozide belongs to the diacylhydrazine class of insecticides that interfere with the 

binding of the endogenous steroidal molting hormone 20-hydroxyecdysone with its nuclear 

receptor protein complex and, as such, is referred to as an ecdysteroid agonist (Dhadilla et al. 1998; 

Shimizu et al. 1997). This non-steroidal ecdysone agonist induces a precocious incomplete molt 

in invertebrates, particularly lepidopterans (e.g., moths). After ingestion of toxic doses, sensitive 

larvae stop feeding and the molting process initiates prematurely leading to desiccation and 

ultimately, death. 

Use Characterization 

Based on the submitted labels, the maximum proposed single application rate for pineapples is 

0.10 lb a.i./acre, and the proposed maximum yearly rate is 0.44 lb a.i./A (Table 1). Intrepid® 2F 

contains 22.6% a.i. and could be applied to pineapples by ground or aerial application equipment. 

The maximum number of applications allowed per year is four. The minimum application interval 

on the proposed label is seven days (Refer to Table 1 below). 

Table 1. Summary use information for methoxyfenozide proposed new use on pineapple, based 

on Intrepid®2F supplemental label (EPA Reg. No. 62719-442).

Use Max. Single 

Application 

Rate 

(lbs. a.i./A)1

Max. No. of 

Applications 

Max. Yearly 

Application 

Rate (lbs. 

a.i./A) 

Min. 

Application 

Interval 

(days) 

Application Method 

Pineapple 0.10 4 0.44 7 Ground spray (foliar)/Aerial 

1

 To be consistent with the maximum yearly application rate (0.44 lb a.i./Acre), EFED used 0.11 lbs ai/A as the 

maximum single application rate. The maximum single application rate is stated on labels as 7 fl oz/A (the label 

states this as 0.10 lb a.i./A) and the maximum annual rate is stated as 28 fl oz/A (the label states 0.44 lb a.i./A). At 2 

lb a.i./gal, that is 0.015 lb a.i./fl oz or 0.109375 lb a.i./7 oz, which rounds off to 0.11 lb a.i./A. Based on these 

calculations, EFED decided to use 0.11 lb a.i./Acre for risk assessment as the maximum application rate.

 

Exposure Characterization 

Environmental Fate and Transport Characterization 

Methoxyfenozide is persistent (t1/2 = 1 to 3 years in soil and water; Goring et al. 1975) and 

moderately mobile (Koc = 219 – 922 L/kgoc in various soils; FAO scale, 2000). It is stable to 

photolysis and hydrolysis (at all pH levels), is not significantly volatile, and degrades very slowly 

by microbial activity. Degradates are predominantly RH-117236 (3,5-dimethylbenzoic acid Ntert-butyl-N’-(3-hydroxy-2-methylbenzoyl)hydrazide) and RH-131154 (3-[N-tert-butyl-N’-(3-
7

methoxy-2-methylbenzoyl)-hydrazinocarbonyl]-5-methylbenzoic acid), although present only in 

low relative amounts (i.e. equivalent to less than 10% of applied radioactivity). Because of its 

resistance to degradation and its moderate mobility, methoxyfenozide has the potential to move 

off the site of application by leaching and/or erosion/runoff, and to accumulate in aquatic systems. 

Table 2 summarizes the physical-chemical properties of methoxyfenozide. For further details on 

the environmental fate and transport of methoxyfenozide, please refer to DP Barcode D249466, 

USEPA (2001a). 

Table 2. General Chemical Properties and Environmental Fate Parameters of 

Methoxyfenozide. 

Chemical/Fate Parameter Value Source Comment

Chemical name n-tert-butyl-N’-[2-methyl-3-

methoxybenzoyl]-3,5-

dimethylbenzohydrazide 

D249466 

Product chemistry data

Molecular mass 368 g/mol D249466 Product chemistry data

Vapor pressure (25C) 2.0 x 10-8 torr D249466 Product chemistry data

Solubility (25C) 3.3 mg/L D249466 

Octanol-water partition coefficient 

(Kow) 5,248 (log Kow =3.72) D249466 

Organic carbon partitioning 

coefficient (Koc) 267, 922, 678, 219, 365 L/kgoc

MRID 441444-33 

Hydrolysis half-life (pH 5, 7, 9) Stable MRID 441444-30 Default 

Aqueous photolysis half-life Stable MRID 446178-05 Default 

Soil photolysis half-life Stable MRID 446178-06 Default 

Aerobic soil metabolism half-life 573, 1100, 772, 336 d MRIDs 446178-08, 

446178-07, 441444-32 

Aerobic aqueous metabolism halflife 387, 962 d MRID 446178-09 

Anaerobic aqueous metabolism 

half-life 654 d MRID 446178-10 

Terrestrial field dissipation half-life 237, 139, 151, 92 d MRID 446178-12, 

446178-11 

 

Measures of Aquatic Exposure 

The estimated environmental concentrations (EECs) in surface water from the proposed use on 

pineapples were generated using EFED’s Tier I aquatic models: The GENeric Estimated 

Environmental Concentration (GENEEC version 2.0, August 2001) model is a Tier 1 computer 

program which uses the soil/water partition coefficient and degradation kinetic data for a pesticide 

to estimate runoff from a 10-hectare field into a 1-hectare by 2-meter deep “standard” pond. This 

model is designed as a coarse screen and estimates conservative pesticide concentrations in surface 
8

water to determine which ones potentially pose sufficient risk to warrant higher-level modeling. 

GENEEC estimates acute, as well as longer-term EEC values and is designed to mimic a Pesticide 

Root Zone Model/Exposure Analysis Model System (PRZM-EXAMS) simulation. The GENEEC 

model considers reduction in dissolved pesticide concentration due to adsorption of pesticide to 

soil or sediment, incorporation, degradation in soil before wash-off to a water body, direct 

deposition of spray drift into the water body, and degradation of the pesticide within the water 

body. An effort was also made to refine aquatic EECs using the Surface Water Concentration 

Calculator (SWCC) tool and is discussed below. 

Input parameters for GENEEC are listed in Table 3. The method of application was obtained from 

the proposed supplemental label (Intrepid® 2F), as well the application rate, retreatment interval 

and buffer zone. The retreatment interval represents the minimum amount of time required 

between applications of the pesticide. Pineapple was modeled using aerial and ground application. 

Spray drift buffer zones of 25 and 150 feet (specified on the proposed label) were used for ground 

and aerial applications, respectively. 

 

Chemical property model input values were chosen in accordance with EFED’s current input 

parameter guidance (USEPA 2009). The upper 90% confidence limit on the mean half-life (960 

d) was selected to represent aerobic soil metabolism and both hydrolysis and photolysis were 

modeled as stable. The upper 90% confidence limit on the mean half-life (1,562 d) was selected 

to represent aerobic aquatic metabolism. In addition, the mean organic carbon partition coefficient 

(Koc) of 490 L/kgoc and aqueous solubility of 3.3 mg/L were incorporated for GENEEC modeling. 

Table 3. GENEEC Chemical-Specific Input Parameters for Methoxyfenozide. 

Table 3. GENEEC (v2.0) input parameter values for methoxyfenozide use on pineapple1.

PARAMETER (units) VALUE(S) SOURCE COMMENT

Application Rate (lb a.i./A) 0.11 Proposed label 

Number of Applications 4 Proposed label 

Interval between Applications (days) 7 Proposed label 

Method of Application Ground/Aerial 

spray 

Proposed label 

Organic Carbon Soil Partition 

Coefficient, KOC (L/kgOC) 

490 MRID: 44144433 Represents the average value among 

four values ranging from 219 to 922 

L/kg. 

Aerobic Soil Metabolism Half-life 

(days) 

960 MRIDs 

44617808, 

44617807, 

4414432 

Represents the 90 percent upper 

confidence limit on the mean of four 

half-life values (695 days). 

Wetted in? No Proposed label 

Depth of Incorporation (inches) 0 Proposed label 
9

Table 3. GENEEC (v2.0) input parameter values for methoxyfenozide use on pineapple1.

PARAMETER (units) VALUE(S) SOURCE COMMENT

Spray Drift Buffer Zone (ft) 25 (ground) 

150 (aerial) 

Proposed label 

Solubility in Water @ 25 OC, 

unbuffered (mg/L or ppm) 

3.3 D249466 – 

Aerobic Aquatic Metabolism Half-life 

(days) 

1562 MRID: 44617809 Represents the 90 percent upper 

confidence limit on the mean of three 

half-life values (674.5 days). 

Hydrolysis Half-life @ pH 7 (days) 0 MRID: 44144430 Stable. 

Aquatic Photolysis Half-life @ pH 7 

(days) 

0 MRID: 44617805 Stable 

1 Parameters are selected as per Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of 

Pesticides; Version 2.1, October 22, 2009. 

Modeling Results 

The EECs for the proposed use on pineapple are listed below in Table 4. Model input/output data 

for these estimates are attached in Appendix A. 

Table 4. Surface Water EECs Based on Methoxyfenozide Use on Proposed New Use on 

Pineapple. 

USE SCENARIO Estimated Environmental Concentrations (EECs, ppb)

Application 

Method Peak 4-day 21-day 60-day 90-day 

Pineapple (GENEEC; rate 

modeled in kg a.i./ha); 0.11 x 

4 applic. @ 7-d interval

Ground 13.5 13.4 13.2 12.7 12.4 

Aerial 13.2 13.2 13.0 12.5 12.2 

Bolded numbers represent the highest EECs among each crop from the uses/scenarios modeled. 

A refined assessment using the SWCC was obtained for comparison and characterization purposes. 

The SWCC estimates pesticide concentrations in surface water that result from pesticide 

applications to land. This model is designed to simulate the environmental concentration of 

pesticide in the water column and sediment for use in regulatory applications by the USEPA Office 

of Pesticides (OPP). The SWCC uses PRZM version 5.0+ (PRZM5) and the Variable Volume 

Water Body Model (VVWM), replacing the older PRZM/EXAMS shell (PE5 shell; last updated 

November 2006), which used PRZM 3 (Carsel et al., 2005) and EXAMS (Burns, 2003). In this 

refinement, the Puerto Rico (PR) coffee scenario was used due to the lack of a specific scenario 

for pineapples grown in Hawaii. The PR coffee scenario was run with different weather files (first 

PR weather, and then two Hawaii weather files were used: Oahu and Maui) to obtain a range of 

EECs. In addition to varying weather files, the curve numbers (CN) were also varied to reflect 

varying levels of runoff and leaching associated with pineapple production (owing primarily to the 

use of plastic mulch). Although pineapple crops are usually associated with soils that leach (i.e., 

they are typically cultivated in sandy soils), which are represented by a CN of 70, they may be 

‘mulched’ with polyethene plastic sheets, which increases runoff and decreases leaching – this is 
10

represented by a CN of 90. Although the SWCC is considered a Tier 2 model, used for refining 

EECs initially derived from GENEEC, the SWCC-generated EECs overlapped with and/or 

exceeded those generated through GENEEC. The results of this analysis can be found in Appendix 

A. Although an effort was made to refine EECs, the exposure estimates did not differ substantially 

from those provided through GENEEC; therefore, the GENEEC values serve as the foundation for 

the risk assessment. 

Aquatic Exposure Monitoring 

 

Methoxyfenozide was not analyzed in monitoring conducted by the U. S. Geological Survey 

(USGS) National Water Quality Assessment (NAWQA) program and is not included in the 

California Department of Pesticide Regulation (CDPR) Surface Water Database (CDPR 2003). 

OPP is not currently aware of other monitoring programs in which methoxyfenozide is an analyte. 

One of the outstanding data requirements for methoxyfenozide was identified in the initial Section 

3 registration: 

Three years after use, obtaining approval for and conducting monitoring of surface water 

and sediment in a representative sample of high use areas in proximity to surface water. 

DAS (Dow Agricultural Science) has agreed to sample for methoxyfenozide over a two-year 

period in lotic (flowing) water bodies (e.g. rivers) and lentic water bodies (e.g. ponds) and 

associated sediment in each of the following states: California, Mississippi, and Michigan, with 

the Agency’s guidance (USEPA 2011). A summary of interim sampling results from this effort is 

provided in Table 5. For more information refer to USEPA, 2013a. The final monitoring report 

was submitted by DAD on April 18, 2014 and it is currently under review. Based on the interim 

results, in flowing water (lotic environments), methoxyfenozide was not detected in any of the 

benthic sediments and in static (lentic) pond environments, the compound was only detected once 

in benthic sediments. In lotic systems, the compound was frequently detected in samples collected 

in California and Mississippi; however, the majority of samples were at or below the limit of 

quantification. For lentic systems, the compound was frequently detected in the water columns of 

samples collected in Michigan and Mississippi; however, again, the majority of samples were at 

or below the limit of quantification (LOQ). Peak residue level in lotic systems ranged as high as 

1 μg/L while in lentic systems, the peak was 0.85 μg/L. 

Table 5. Summary of Interim Sampling Results for Methoxyfenozide in Lotic and Lentic 

Water Column and Associated Benthic Sediments 

State Parameters 

Lotic Lentic 

Water (μg/L) Sediment 

(μg/kg) Water (μg/L) Sediment (μg/kg) 

CA 

Detects/Samples 

Range 

Mean/Median 

72/72 

0.018 – 1.0 

0.14/0.061 

0/4 

- 

- 

1/10 

0.017 

- 

0/10 

- 

- 

MI Detects/Samples 

Range 

0/14 

- 

0/2 

- 

8/11 

0.025 – 0.85 

1/11 

3.4 
11

Mean/Median - - 0.19/0.06 - 

MS 

Detects/Samples 

Range 

Mean/Median 

38/48 

0.016 – 0.181 

0.036/0.025 

0/4 

- 

- 

8/10 

0.019 – 0.233 

0.056/0.024 

0/10 

- 

- 

For water, the limit of detection (LOD) was 0.015 μg/L and the limit of quantitation (LOQ) was 0.05 μg/L. Values between the 

LOQ and LOD are in italic. For sediment, the LOD was 3 μg/kg and the LOQ was 10 μg/kg. 

Measures of Terrestrial Exposure 

T-REX1

 (Version 1.3.1) is used to calculate dietary EECs for estimating exposure to birds and 

mammals resulting from the proposed use of methoxyfenozide. Upper-bound Kenega nomogram 

values are used to derive EECs for methoxyfenozide exposures to birds based on dietary-based 

exposure. A one year time period is simulated. The default foliar half-life of 35 days was used for 

modeling the proposed uses. An example printout from the T-REX model is provided in Appendix 

C. Risks to terrestrial plants were not assessed. 

Ecological Effects Characterization 

Appendix B provides a full listing of the ecological effect data that have been submitted for 

methoxyfenozide. 

Aquatic Effects Characterization

Based on the most sensitive toxicity endpoints, methoxyfenozide is classified as moderately toxic 

to freshwater fish (and to aquatic-phase amphibians, for which freshwater fish serve as surrogates), 

estuarine/marine invertebrates and estuarine/marine fish, and as very highly toxic to freshwater 

invertebrates on an acute exposure basis (Table 7). In some cases the acute toxicity endpoint is 

non-definitive and suggests that the potential acute toxicity of methoxyfenozide to these species 

may be limited by the chemical’s solubility (3.3 mg/L at 25o

C). Toxicity data show effects on 

survival in freshwater fish exposed to methoxyfenozide on a chronic exposure basis. The midge 

(Chironomus riparius), a freshwater benthic invertebrate, was the most sensitive species tested on 

a chronic exposure basis, and resulted in delayed emergence and development of the species (at 

the LOAEC of 0.013 mg a.i./L, only 45% of the midges emerged, and these developed slower than 

controls). Chronic toxicity data in fish indicate that freshwater fish [fathead minnow Pimephales 

promelas, NOAEC=0.53 mg a.i./L (based on survival)] are more sensitive than marine/estuarine 

fish [sheepshead minnow, Cyprinodon variegatus, NOAEC=1.5 mg a.i./L (based on growth)] to 

methoxyfenozide. No acute toxicity data are available for midge larvae; therefore, an acute-tochronic ratio (ACR) was used to calculate an acute freshwater invertebrate endpoint using acute 

and chronic toxicity data from another aquatic invertebrate, i.e., the freshwater waterflea (Daphnia 

magnia)

2

. This results in an estimated EC50 of 0.06 mg a.i./L for the midge3. 

 

1

 USEPA. 2014. T-REX Version 1.5.2 (Terrestrial Residue Exposure). http://www.epa.gov/oppefed1/models/terrestrial/#trex (last accessed 

03.25/14) 

2

 The most sensitive acute and chronic endpoints available for daphnids are an EC50 of 3.7 mg a.i./L (MRID 441444-

11) and a NOAEC of 0.20 mg a.i./L (MRID 446177-14), respectively. 

3

 [(3.7 mg a.i./L)/(0.20 mg a.i./L) = (0.06 mg a.i./L)/(0.0031 mg a.i./L)] 
12

The registrant has submitted data (MRID 489387-01) examining the effects of chronic exposure 

to methoxyfenozide on the development of African clawed frogs (Xenopus laevis) in response to 

uncertainties regarding potential impacts on the hypothalamic-pituitary-thyroid axis (HPT) based 

on chronic mammalian toxicity data. EFED has not yet completed the review process for the 

amphibian study, but preliminary results indicate that methoxyfenozide has effects on thyroid 

histology at 0.0747 mg a.i./L under flow-through conditions.

The freshwater green algae (Pseudokirchneriella subcapitata) was the most sensitive aquatic nonvascular plant tested, but the endpoint was non-definitive, i.e., the effect concentration for 50% 

mortality of the algae exceeded the highest concentration tested (EC50>3.4 mg a.i./L), suggesting 

that the chemical’s solubility may limit its impacts on aquatic non-vascular plants. Data on the 

effects of methoxyfenozide on vascular plants are not available. 

For estuarine/marine invertebrates, chronic toxicity data are available for the mysid shrimp 

(Americamysis bahia). In this study, reduced growth (length) occurred, with a NOAEC of 0.025 

mg a.i./L. 

The registrant submitted data on red swamp crayfish (Procambarus clarkia) to address uncertainty 

whether other aquatic organisms that molt may be sensitive to methoxyfenozide. Exposure of 

crayfish to methoxyfenozide did not affect survival, growth (length or weight), total number of 

molts or number of molts per females in crayfish (EC50: >0.190 mg a.i./L; NOAEC: 0.190 mg 

a.i./L; MRID 457027-02). The study is scientifically sound; however, it is classified as 

supplemental because it is a non-guideline study. 

Terrestrial Effects Characterization 

Methoxyfenozide is classified as practically non-toxic to birds (as well as reptiles and terrestrialphase amphibians, for which birds serve as surrogates) on both an acute oral and subacute dietary 

exposure basis; the compound is practically non-toxic to mammals on an acute oral exposure basis. 

In a reproductive toxicity study in bobwhite quail (Colinus virginianus; MRID 446177-11), 

methoxyfenozide caused a statistically significant difference in eggshell thickness compared to 

untreated controls. Across the dietary treatment levels of methoxyfenozide tested, declines in 

eggshell thickness were accompanied with increases in the number of eggs cracked, although the 

increase in the number of eggs cracked was not statistically significant. The endpoint of eggshell 

thinning observed at the LOAEC (780 mg/kg-diet) was used to calculate chronic risk to birds 

(NOAEC=520 mg/kg-diet). No other effects were observed in chronic toxicity studies with birds. 

In mammals, chronic exposure to rats adversely affected survival at the 20,000 ppm dose level 

(LOAEC, highest dose tested) in a 2-year combined chronic toxicity/carcinogenicity study (MRID 

446177-31). The NOAEC from this study is 8,000 ppm. 

Methoxyfenozide is classified as “practically non-toxic” to adult honey bees (Apis mellifera; Table 

8), but has been shown to be highly toxic to target lepidopteran pests on an acute dietary exposure 

basis (European corn borer, Ostrinia nubilalis: LC50=0.009 ppm; Trisyono and Chippendale 1997). 
13

Although methoxyfenozide is intended to target lepidopterans, there is uncertainty regarding the 

extent to which other species of insects and taxa dependent on ecdysone may be affected. Because 

of methoxyfenozide’s mode of action, larval insects, including larval honey bees, may be more 

sensitive to methoxyfenozide than are adult insects. To address this uncertainty honey bee larval 

toxicity data were required by EPA. In a 21-day honey bee brood study (MRID 450655-01) with 

formulated product (RH 2485 SC 240), there were no significant effects on brood development 

following exposure of the bee colony to a formulation of methoxyfenozide (101 mg formulated 

product/L) via spiked sugar solution. The registrant has submitted additional studies on honey bee 

brood development and on methoxyfenozide residues in bee colonies from almonds treated with 

methoxyfenozide at bloom to further address this uncertainty (MRIDs 489622-01, 489622-02, 

489622-03). While EFED has not yet completed the review process for these studies, preliminary 

results indicate that exposure to methoxyfenozide did not result in adverse effects to honey bee 

larvae and pupae development, or to colony overwintering survival, although uncertainties have 

been identified in these studies. 

No data are available to assess the effects of methoxyfenozide on terrestrial plants. However, given 

the mode of action of the compound (insect growth regulator) and the lack of toxicity observed in 

non-vascular aquatic plants, as well as a lack of reported plant incidents for methoxyfenozide, 

toxicity data for terrestrial plants are not needed. 

Table 7. Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for 

Methoxyfenozide 

Taxonomic 

Group 

Study 

Type Surrogate Species 

Toxicity Value 

(all units in 

terms of 

measured active 

ingredient) 

Acute 

Toxicity 

Classification 

Source 

(MRID) 

Study 

Classification 

Freshwater 

Fish 

96-Hour 

Acute 

Toxicity 

Rainbow trout 

Oncorhynchus 

mykiss

LC50>4.2 mg 

a.i./L 

(No mortality at 

the highest 

treatment level 

tested) 

Moderately 

Toxic 441444-10 Acceptable 

Full Life 

Cycle 

Toxicity 

Fathead minnow 

Pimephales 

promelas

NOAEC=0.53 mg 

a.i./L 

LOAEC=1.0 mg 

a.i./L (survival) 

N/A 446177-16 Acceptable 

Freshwater 

Invertebrates 

Estimate 

based on 

Acute-toChronic 

Ratio1

Midge 

Chironomus 

riparius

EC50 = 0.061 mg 

a.i./L 

(mortality) 

Very highly 

toxic N/A1 N/A 

Chronic 

Effects on 

Midge 

Larvae 

NOAEC=0.0031 

mg a.i./L 

LOAEC=0.0063 

mg a.i./L 

(Delayed 

emergence and 

development) 

N/A 450328-01 Supplemental 
14

Taxonomic 

Group 

Study 

Type Surrogate Species 

Toxicity Value 

(all units in 

terms of 

measured active 

ingredient) 

Acute 

Toxicity 

Classification 

Source 

(MRID) 

Study 

Classification 

Estuarine/ 

Marine Fish 

96-Hour 

Acute 

Toxicity 

Sheepshead minnow 

Cyprinodon 

variegatus

96-hr LC50 >2.8 

mg a.i./L 

Moderately 

Toxic 441444-12 Acceptable 

Early Life 

Stage 

Toxicity 

NOAEC = 1.5 mg 

a.i./L 

LOAEC = 2.6 mg 

a.i./L 

(growth) 

N/A 446177-12 Acceptable 

Estuarine/ 

Marine 

Invertebrates 

96-Hour 

Shell 

Deposition 

Eastern oyster 

Crassostrea 

virginica

96-hr EC50 = 1.2 

mg a.i./L 

Moderately 

Toxic 441444-13 Acceptable 

Invertebrate 

Life Cycle 

Toxicity

Mysid 

Americamysis bahia 

(formerly

Mysidopsis bahia)

NOAEC = 0.025 

mg a.i./L 

LOAEC = 0.051 

mg a.i./L 

(Reduced 

growth/length) 

N/A 446177-15 Acceptable 

NonVascular 

Aquatic 

Plants 

5-Day 

Toxicity 

Test 

Freshwater alga 

Pseudokirchneriella 

subcapitata 

(formerly

Selenastrum 

capricornutum)

EC50 >3.4 mg 

a.i./L 

NOAEC= 3.4 mg 

a.i./L 

No effects at the 

highest treatment 

level tested 

N/A 446177-18 Acceptable 

1 Acute-to-Chronic Ratio (ACR) was used to estimate the acute toxicity for the midge using the ratio of acute to chronic data points from studies 

with Daphnia and the chronic NOAEC from the midge lifecycle test. [(3.7 mg a.i./L)/(0.20 mg a.i./L) = (0.06 mg a.i./L)/(0.0031 mg a.i./L)] 

Table 8: Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for 

Methoxyfenozide 
15

Taxonomic 

Group Study Type Surrogate Species 

Toxicity Value 

(all units in 

terms of 

measured active 

ingredient) 

Acute Toxicity 

Classification Source 

(MRID) 

Study 

Classification 

Birds 

Acute Oral 

Toxicity 

Northern 

bobwhite quail

Colinus 

virginianus 

LD50 >2,250 mg 

a.i./kg-bw 

No effects at 

highest treatment 

level tested

Practically 

Non-Toxic 441444-06 Acceptable 

Subacute 

Dietary 

Toxicity 

Northern 

bobwhite quail

Colinus 

virginianus 

LC50 >5,870 

mg a.i./kg-diet 

No effects at 

highest treatment 

level tested 

Practically 

Non-Toxic 441444-07 Acceptable 

Avian 

Reproductiv

e Toxicity 

Northern 

bobwhite quail

Colinus 

virginianus 

NOAEC=520 mg 

a.i./kg-diet 

(Reduction in 

eggshell 

thickness) 

N/A 446177-11 Acceptable 

Mammals 

Acute oral 

Toxicity 

Rat 

Rattus 

norvegicus 

LD50 >5,000 mg 

a.i./kg-bw 

Acute Toxicity 

Category 4 441444-15 Acceptable 

Chronic 

Dietary 

Toxicity 

Rat 

Rattus 

norvegicus 

NOAEC =8,000 

ppm diet 

(survival) 

N/A 446177-31 Acceptable 

Terrestrial 

Invertebrates 

Acute 

Contact 

Toxicity Honey bee 

Apis mellifera 

LD50 >100 μg 

a.i./bee 

Practically 

Non-Toxic 441444-29 Acceptable 

Oral 

Toxicity 

LC50 > 100 μg 

a.i./bee 

Practically 

Non-Toxic 446177-17 Supplemental 
16

Taxonomic 

Group Study Type Surrogate Species 

Toxicity Value 

(all units in 

terms of 

measured active 

ingredient) 

Acute Toxicity 

Classification Source 

(MRID) 

Study 

Classification 

Brood NOAEL=101 mg 

a.i./L N/A 450655-01 Supplemental 

1 Birds represent surrogates for terrestrial-phase amphibians and reptiles. 

4.3. Ecological Incidents 

The ecological incident information system (EIIS) is a database maintained by the Office of 

Pesticide Programs; the database contains ecological incidents that have been reported to the 

Agency. When available, EIIS includes date and location of an incident, type and magnitude of 

effects observed in various species, use(s) of pesticides known or suspected of contributing to the 

incident, and results of any chemical residue analysis or other analyses conducted during incident 

investigation. EIIS incidents are categorized according to the certainty that the incident resulted 

from pesticide exposure. The Avian Incident Monitoring System (AIMS)4

 is a database 

administered by the American Bird Conservancy that contains publicly available data on reported 

avian incidents involving pesticides. Many of the incidents listed in this database are also in the 

EIIS. Because of uncertainties regarding the extent to which incidents are reported to EPA, the 

absence of incident reports cannot be construed as the absence of incidents. 

EIIS contains five incidents for methoxyfenozide. All five incidents reported bee kills in which 

methoxyfenozide was mentioned. Four reported incidents took place in California, and one in 

New York State. For all of these incidents, more than one pesticide was named along with 

methoxyfenozide. Since methoxyfenozide alone is not acutely toxic to adult bees on an acute 

contact or oral exposure basis and since these beekill incidents involved the loss of adult bees, it 

is uncertain that methoxyfenozide was the cause of these losses. Also, preliminary analysis of 

available toxicity data on the chronic effects of methoxyfenozide on honey bee brood do not 

indicate adverse effects on developing bees at the exposure concentrations tested. EPA does not 

have toxicity data nor does it conduct risk assessments for tank mixes of different chemicals or 

combinations of active ingredients. It is therefore unknown whether methoxyfenozide’s potential 

toxicity to bees is enhanced or otherwise affected by other chemicals that may be tank mixed with 

it or sprayed concurrently. 

In the Office of Pesticide Programs’ Aggregate Incident Reports, there were no incidents attributed 

to methoxyfenozide. AIMS was also searched on March 11, 2014 and revealed no incidents to 

birds associated with methoxyfenozide. 

Table 9. Summary of Methoxyfenozide Incidents 

 

4

 American Bird Conservancy. 2014. Avian Incident Monitoring System. 

http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/login.cfm 
17

Chemical 

Name 

(Product 

Name) 

Crop 

Incident 

Data 

System 

Number 

Date Certainty Location Affected Taxa Application 

Method 

Methoxyfenozide 

(Intrepid® 2F) 

Pistachios I023107-

019 

July 

2011 Unlikely California Honey bees 

(92 colonies) Ground 

Almonds 

I024029-

001 February 

2012 Unlikely California Honey bees (464 colonies) Unknown 

Orchard/ 

Corn 

Planting 

I024270-

001 May 

2012 Unlikely New York Honey bees 

(48 colonies) 

Corn planted with 

air planter 

Almonds 

I025162-

001 February 

2013 Unlikely California Honey bees (464 colonies) Unknown 

Almonds I026240-

001 

February 

2014 Possible California Honey bees 

(7,800 colonies) Ground 

Risk Characterization 

Risk Estimation 

 Aquatic Organisms 

In the acute freshwater fish, acute estuarine/marine fish, and non-vascular aquatic plant toxicity 

studies submitted, there were no mortality or sub-lethal effects at the highest treatment levels tested 

(i.e., LC50, endpoints are ‘greater than’ values); therefore, these endpoints are not used to calculate 

risk quotient (RQ) values. However, the information in these studies was used to help characterize 

potential risk in the Risk Description section of this assessment. 

The RQs for freshwater invertebrates exceed the Agency’s levels of concern (LOCs) for listed 

species based on acute exposure (LOC=0.05) and for listed and non-listed species based on chronic 

exposure (LOC=1) for the proposed use (Table 10). For estuarine/marine invertebrates, RQs for 

the proposed pineapple use do not exceed the Agency’s acute or chronic risk LOCs for either listed 

or non-listed species. 

Table 10. Acute and Chronic RQ Values for Freshwater and Estuarine/Marine 

Invertebrates from the Proposed Use of Methoxyfenozide on Pineapples. 

Use Site (Scenario) Exposure 

Type EEC (μg a.i./L) Freshwater Invertebrate RQ1

Estuarine/Marine 

Invertebrate RQ2

Pineapple 

(ground application) 

Acute 13.5 (peak) 0.24* 0.011 

Chronic 13.2 (21-day) 4.3 0.53 

Pineapple 

(aerial application) 

Acute 13.2 (peak) 0.23* 0.011 

Chronic 13.0 (21-day) 4.2 0.52 1 Based on an ACR-calculated LC50 of 0.06 mg a.i./L (57 μg a.i./L) (midge, Chironomus riparus) and a NOAEC of 

0.0031 mg a.i./L (3.1μg a.i./L ) (midge, Chironomus riparus). 2

 Based on an EC50 of 1.2 mg a.i./L (1200 μg a.i./L) (Eastern oyster, Crassostrea virginica) and a NOAEC of 0.025 

mg a.i./L (25 μg a.i./L) (mysid, Americamysis bahia). 

Bolded numbers exceed the Agency’s LOC for non-listed (i.e, RQ≥0.5) and listed species (i.e., RQ≥0.05); bolded 

with * exceeds Agency’s LOC for listed species only. 
18

As stated above, acute risk to either freshwater fish or estuarine/marine fish from methoxyfenozide 

was not assessed since the 96-hr LC50 value exceeded the highest concentration tested, and no 

mortality was observed at the highest concentration. Chronic risk for freshwater fish was assessed 

using the most sensitive NOAEC of 530 μg a.i./L (based on reduced survival) for the fathead 

minnow, and chronic risk for marine/estuarine fish was assessed using the most sensitive NOAEC 

of 1500 μg a.i./L (growth) for the sheepshead minnow. None of the chronic RQs for fish 

(freshwater or marine/estuarine) exceed the Agency’s chronic risk LOC (RQ≥1.0) for the proposed 

uses (Table 11). 

Table 11. Chronic RQ Values for Marine/Estuarine and Freshwater Fish from the 

Proposed Use of Methoxyfenozide on Pineapple

Use Site (Scenario) EEC (μg a.i./L) Freshwater Fish RQ1 Marine/Estuarine 

Fish RQ2

Pineapple 

(ground application) 12.7 (60-day) 0.024 0.008 

Pineapple 

(aerial application) 12.5 (60-day) 0.024 0.008 

1. Based on a NOAEC of 530 μg a.i./L (fathead minnow, Pimephalas promelus). 

2. Based on a NOAEC of 1500 μg a.i./L (sheepshead minnow, Cyprinodon variegatus). 

 Terrestrial Organisms 

In the avian acute and sub-acute toxicity studies submitted, there were no mortality or sub-lethal 

effects at the highest treatment levels tested (i.e., the acute oral LD50 and sub-acute dietary LC50

values are ‘greater than (>)’ values); therefore, these endpoints are not used to calculate RQ values. 

However, the information in these studies was used to help characterize risk in the ‘Risk 

Description’ section of this assessment. For chronic risk, RQs for birds in several forage categories 

are all below the Agency’s chronic risk LOC (RQ≥1.0) for the proposed use (RQs range from 0.17 

to 0.01) (Table 12). 

Table 12. Dietary-based Upper-Bound Avian Chronic EEC and RQ Values for Proposed 

Methoxyfenozide Use on Pineapple.

Application 

Method 

Dietary-Based EECs and RQs1

Short Grass Tall Grass Broadleaf Plants/ 

Small Insects 

Fruits/Pods/ 

Seeds/ 

Large Insects 

EEC2 RQ EEC RQ EEC RQ EEC RQ 

Use Site/Crop Group (Max. Single Application Rate)

Pineapple (0.11 lb a.i./A)

Ground/Aerial 86.81 0.17 39.79 0.08 48.83 0.09 5.43 0.01 1

 Based on a NOAEC of 520 mg a.i./kg-diet (Northern bobwhite quail, Colinus virginianus). 2 From T-REX, Version 1.5.2. See Appendix C for details.

In the available mammalian acute toxicity studies, there were no mortality or sublethal effects at 

the highest treatment levels tested (i.e., the acute oral LD50 is a ‘greater than (>)’ value); therefore, 
19

these endpoints are not used to calculate RQ values. However, information from the studies was 

used to help characterize risk in the ‘Risk Description’ section of this assessment. 

In mammals, chronic exposure to rats decreased survival at the 20,000 ppm dose level (LOAEC, 

highest dose tested) in a 2-year combined toxicity/carcinogenicity study (MRID 446177-31). The 

NOAEC from this study is 8,000 ppm. Chronic RQs for mammals were calculated by comparing 

the NOAEC (8,000 mg a.i./kg-diet) to upper-bound exposure values from T-REX. Dietary-based 

chronic RQs for mammals are all below the LOC (1.0) for chronic mammalian risk (Table 13). 

Dose-based RQs for mammals are also below the chronic risk LOC for mammals (ranging from 

<0.01 to 0.02) (Table 14). See Appendix C for details. 

Table 13. Dietary-based Upper-Bound Mammalian Chronic EEC and RQ Values for 

Proposed Methoxyfenozide Use on Pineapple.

Application 

Method 

Dietary-Based EECs and RQs1

Short Grass Tall Grass Broadleaf Plants/ 

Small Insects 

Fruits/Pods/ 

Seeds/ 

Large Insects 

EEC2 RQ EEC RQ EEC RQ EEC RQ 

Use Site/Crop Group (Max. Single Application Rate)

Pineapple (0.11 lb a.i./A)

Ground/Aerial 86.81 <0.01 39.79 <0.01 48.83 <0.01 5.43 <0.01 1

 Based on a NOAEC of 8,000 mg a.i./kg-diet (rat). 2 From T-REX, Version 1.5.2. See Appendix C for details.

 
20

Table 14. Dose-based Upper-Bound Mammalian Chronic EEC and RQ Values for 

Proposed Methoxyfenozide Use on Pineapple.

Application 

Method: 

Ground/Aerial 

Dose-Based EECs and RQs1

Short Grass Tall Grass Broadleaf Plants/

Small Insects 

Fruits/Pods/ 

Seeds/ 

Large Insects 

Seeds 

EEC2 RQ EEC RQ EEC RQ EEC RQ EEC RQ 

Use Site/Crop Group (Max. Single Application Rate) 

Pineapple (0.11 lb a.i./A) 

Mammalian 

Size Class 

 

15 g 82.76 0.02 37.93 0.01 46.55 0.01 5.17 <0.01 1.15 <0.01 

35 g 57.20 0.02 26.22 0.01 32.18 0.01 3.58 <0.01 0.79 <0.01 

1000 g 13.26 0.01 6.08 0.01 7.46 0.01 0.83 <0.01 0.18 <0.01 

1

 Based on adjusted NOAELs, that were in turn based on a NOAEC of 8,000 mg a.i./kg-diet (rat). 2 From T-REX, Version 1.5.2. See Appendix C for details.

EFED does not currently estimate RQs for non-listed terrestrial non-target invertebrates. As noted 

previously, methoxyfenozide is classified as ‘practically non-toxic’ to adult honey bees but has 

been shown to be very toxic to target lepidopteran species such as the European corn borer (which 

is a common lepidopteran pest of corn) on an acute dietary exposure basis (Trisyono and 

Chippendale 1997). Screening-level risk assessments do not typically evaluate risks to terrestrial 

invertebrates; however, toxicity information for beneficial insects is used to develop precautionary 

label language where necessary. Based on the available data from adult honey bees, precautionary 

label language for bees does not appear necessary and current labels do not have a bee warning. 

As stated earlier, the registrant has submitted additional studies on honey bee brood development 

and on methoxyfenozide residues in bee colonies from almonds treated with methoxyfenozide at 

bloom (MRIDs 489622-01, 489622-02, 489622-03). While EFED has not yet completed the 

review process for these studies, preliminary results indicate that exposure to methoxyfenozide 

does not result in adverse effects to honey bee larvae and pupae development, or to colony 

overwintering survival, although uncertainties have been identified in the submitted studies. 

Risk Description 

Methoxyfenozide is characterized as persistent and moderately mobile and is expected to move 

into surface water through run-off and spray drift following application. The results of this 

screening-level risk assessment indicate that the proposed new use of methoxyfenozide on 

pineapples has the potential for direct adverse effects on listed and non-listed freshwater 

invertebrates. The RQs for freshwater invertebrates exceed the Agency’s LOCs for acute risk to 

listed species and LOCs for chronic risk to listed and non-listed species for the proposed use on 

pineapple. These results are based on EECs derived for maximum-labeled spray application rates 

for the proposed use. The likelihood of direct adverse effects to birds, mammals, fish, and 

terrestrial and aquatic plants and estuarine/marine invertebrates from exposure to methoxyfenozide 
21

as a result of the proposed use on pineapples is expected to be low. However, the extent to which 

other taxa that may depend on freshwater aquatic invertebrate species may be indirectly affected 

is uncertain. 

Risks to Aquatic Organisms

Methoxyfenozide is characterized as moderately toxic to freshwater fish, estuarine/marine 

invertebrates and estuarine/marine fish and highly toxic to freshwater invertebrates on an acute 

exposure basis. Acute toxicity risk estimates were non-definitive (i.e., the EC or LC50 values 

exceeded the highest concentration tested) for freshwater and estuarine/marine fish and aquatic 

nonvascular plants and suggest that the toxicity of the compound to these taxa may be limited by 

its solubility

Aquatic exposure estimates are based on EECs obtained by GENEEC modeling. GENEEC EECs 

are typically regarded as representing conservative estimates of exposure because the input value 

for the application rate is the labeled maximum, the entire watershed is assumed to be cropped and 

treated, runoff is assumed to be from a 6-inch rainfall over a 24-hour period, and the geographic 

location of use is regarded as representative of high-end potential for pesticide runoff and is not 

necessarily representative of runoff conditions for the labeled use. However, when a refined 

assessment using SWCC was obtained for comparison purposes (See Appendix A), the refined 

EECs overlapped and/or exceeded those generated using GENEEC and did not substantially 

change risk estimates. 

For freshwater invertebrates, RQ values (using GENEEC EECs) exceed the Agency’s acute listed 

species LOC (0.05), when conservative runoff assumptions (CN=90) are used in the SWCC 

modeling runs, the LOC is exceeded for both listed and non-listed for freshwater aquatic 

invertebrates species. That said, there is some uncertainty in the acute risk to invertebrates since 

the EC50 was calculated using an ACR (to represent the more sensitive midge) based on the ratio 

of acute-to-chronic toxicity for the freshwater invertebrate D. magna. For comparison, if RQs for 

freshwater invertebrates are calculated using the D. magna EC50 of 3.7 mg a.i./L and the NOAEC 

of 0.20 mg a.i./L for D. magna, LOCs are not exceeded (acute RQ=0.004, chronic RQ=0.07) using 

the conservative EECs derived using GENEEC. Risk estimates for marine/estuarine invertebrates 

do not exceed acute or chronic risk LOCs for listed or non-listed species. 

Because there were no mortalities or sub-lethal effects at the highest treatment levels tested in the 

freshwater fish and estuarine/marine fish acute toxicity studies, RQ values for acute exposures 

were not calculated in the Risk Estimation section of this assessment. In order to gain a better 

understanding of how the EECs for the maximum proposed application rate relate to the toxicity 

data currently available for these taxa, RQs were calculated using the conservative assumption that 

the highest concentrations tested in the toxicity studies represent endpoints [i.e., LC50 = 4.2 mg 

a.i./L (freshwater fish); LC50 = 2.8 mg a.i./L (estuarine/marine fish)]. A similar assumption was 

made for aquatic plants (EC50 = 3.4 mg a.i./L for freshwater algae). As stated earlier, in some 

cases the non-definitive acute toxicity endpoint suggests that the potential acute toxicity of 

methoxyfenozide may be limited by the chemical’s solubility (3.3 mg/L at 25oC). Using the peak 
22

aquatic EEC for ground application (0.0135 mg a.i./L), all of these acute RQs are below the 

Agency's acute risk LOCs (freshwater fish RQ = 0.003; estuarine/marine fish RQ = 0.005; 

freshwater algae RQ = 0.004). The actual RQs would be lower because no effects were observed 

at the highest treatment levels tested. Additionally, based on the results of EFED’s risk assessment 

(using the GENEEC EECs) for the proposed use, the chronic RQ values for fish (freshwater and 

estuarine/marine) do not exceed the Agency’s LOCs for listed or non-listed species. 

Therefore, the likelihood of direct adverse effects to fish and aquatic plants and estuarine/marine 

invertebrates from exposure to methoxyfenozide as a result of the proposed use on pineapples is 

expected to be low. However, the extent to which other taxa that may depend on freshwater aquatic 

invertebrate species may be indirectly affected is uncertain. 

No data are available to assess the potential risks of methoxyfenozide exposure to aquatic vascular 

plants; however, given the mode of action of methoxyfenozide as an insect growth regulator and 

that toxicity data for nonvascular aquatic plants did not demonstrate adverse effects up to the 

solubility limit (3.3 mg/L) of the compound, the current information does not suggest that there 

would be adverse effects on plants. Finally, there are no reported plant incidents in EFED’s 

incident databases. 

Risks to Terrestrial Organisms

On an acute exposure basis, methoxyfenozide is classified as practically non-toxic to birds, 

mammals and adult honey bees. 

Because no mortality or sub-lethal effects were observed at the highest treatment levels tested in 

the avian acute oral and sub-acute dietary studies, standard RQ values were not calculated in the 

Risk Estimation section of this assessment. In order to gain a better understanding of how the EECs 

for the maximum proposed methoxyfenozide application rates relate to the toxicity data currently 

available for birds, the T-REX model was used to calculate RQs using the conservative assumption 

that the highest values tested in the avian studies represent endpoints [i.e., acute oral LD50 = 2,250 

mg/kg-bw (bobwhite quail) and sub-acute dietary LC50 = 5,870 mg/kg diet (bobwhite quail)]. In 

this analysis, none of the RQs exceeds the Agency’s acute risk LOC for listed (LOC=0.1) or nonlisted species (LOC = 0.5). The actual RQs would be lower than these because no effects were 

observed at the highest treatment levels tested. And as discussed previously in the Risk Estimation 

section, for chronic risk, RQs for birds in several forage categories are all below the Agency’s 

chronic risk LOC (Table 12). 

Therefore, the potential for adverse effects to birds from acute, sub-acute, or chronic exposure to 

methoxyfenozide from the proposed new uses is considered low. However, the extent to which 

birds that depend on freshwater aquatic invertebrate species may be indirectly affected is uncertain. 

For mammals, because there was no mortality or sub-lethal effects at the highest treatment levels 

tested in the acute oral toxicity study with rats, the standard acute and RQ values were not 

calculated in the Risk Estimation section of this assessment. Calculating RQs using the 

conservative assumption that the highest value tested in the acute toxicity study represents the 
23

endpoint (i.e., acute oral LD50 =5,000 mg/kg-bw), results in acute RQs <0.01 for the proposed use 

on pineapple. Therefore, the acute RQs in this analysis do not exceed the Agency’s acute risk 

LOCs for mammals. The actual RQs would be lower than these since no acute mortality effects 

were actually identified at the highest treatment levels tested. 

In mammals, chronic exposure to rats adversely affected survival at the 20,000 ppm dose level 

(LOAEC, highest dose tested) in a 2-year combined chronic toxicity/carcinogenicity study (MRID 

446177-31). The NOAEC from this study is 8,000 ppm. 

Chronic risk to mammals can be estimated by comparing the NOAEC (8,000 mg a.i./kg-diet) to 

upper-bound exposure values from T-REX. Assuming exposure to mammals from the proposed 

use on pineapple, which results in the highest (most conservative) EECs, the highest RQ is 0.09, 

which does not exceed the chronic risk LOC (1.0). See Appendix C for details. 

Therefore, the likelihood of direct adverse effects to mammals from acute exposure to 

methoxyfenozide from the proposed new use is considered low. Additionally, the likelihood of 

adverse effects on mammals from chronic exposure is considered low. 

No data are available to assess the potential risks of methoxyfenozide exposure to terrestrial plants; 

however, given the mode of action of methoxyfenozide as an insect growth regulator, there is 

uncertainty whether the compound may have any effects on plants. Also, there are no reports of 

plant damage resulting from exposure to methoxyfenozide in EFED’s incident data bases. 

 

Terrestrial Invertebrates 

EFED does not currently estimate RQs for non-listed terrestrial non-target invertebrates. Based on 

the acute contact and acute oral toxicity studies with young adult honey bees, the LD50 for 

methoxyfenozide is >100 μg/bee. Therefore, the potential for direct adverse effects to adult honey 

bees is considered low. Although larval insects are expected to be more sensitive to 

methoxyfenozide than adults based on the mode of action of the compound, available data on the 

effects of methoxyfenozide on honey bee brood development do not indicate any significant effects 

up to 101 mg a.i./L based on a 21-day feeding study examining larval development through adult 

emergence (MRID 489622-01). A preliminary review of data on the toxicity of methoxyfenozide 

to honey bee colonies does not indicate that the compound adversely affects overwintering survival 

of bees. 

Federally Threatened and Endangered (Listed) Species Concerns 

Based on this screening-level assessment, there are potential acute risks to the listed freshwater 

invertebrates from the proposed new use of methoxyfenozide on pineapple at the maximum 

application rate (Table 16). According to EFED’s LOCATEs data base5 for endangered and 

threatened species, two of the invertebrate species in Hawaii/pineapple area are listed as aquatic: 

the Kauai cave amphipod and Newcomb’s snail. Additionally, five listed species of damselfly 

 

5

 LOCATES=Locations of Crops and Endangered and Threatened Species, Version 2.3. 
24

insects have aquatic larval stages that would be of concern (see Appendix D for LOCATES 

report). 

Because of the potential risk from direct effects to the listed invertebrates described above, should 

exposure occur, it is uncertain whether listed species of all taxa may potentially be affected 

indirectly due to alterations in their habitat (e.g., food sources, shelter, and areas to reproduce). 

Table 16. Listed Species Risks Associated with Potential Direct or Indirect Effects Due to the 

Proposed Use of Methoxyfenozide on Pineapple. 

LISTED TAXON DIRECT EFFECTS* 

Terrestrial and semi-aquatic plants - monocots Not assessed 

Terrestrial and semi-aquatic plants - dicots Not assessed 

Aquatic Insects Yes (acute) 

Birds No 

Terrestrial-phase amphibians No 

Reptiles No 

Mammals No 

Aquatic plants No 

Freshwater fish No 

Aquatic-phase amphibians No 

Freshwater crustaceans Yes (acute) 

Mollusks No 

Marine/estuarine fish No 

Marine/estuarine crustaceans No 

*The acute risk to listed species LOC was exceeded for freshwater invertebrates. Therefore, the potential for indirect 

adverse effects to those species that rely on a specific animal species (specifically freshwater invertebrates, 

estuarine/marine invertebrates, and/or terrestrial invertebrates) or multiple animal species (specifically freshwater 

invertebrates, estuarine/marine invertebrates, and/or terrestrial invertebrates) are uncertain. Indirect effects may 

include general habitat modification, host plant loss, and food supply disruption. 
25

Conclusions for Proposed New Use 

In this action, methoxyfenozide is proposed to be used as a foliar spray on pineapples. 

Based on the maximum application rate for the proposed use, methoxyfenozide has the potential 

for direct effects to listed freshwater invertebrate species after acute exposure and direct effects to 

listed and non-listed freshwater invertebrate species following chronic exposure. 

The likelihood of direct adverse effects to birds, mammals, fish, and terrestrial and aquatic plants 

and estuarine/marine invertebrates from exposure to methoxyfenozide as a result of the proposed 

use on pineapples is expected to be low. However, the extent to which other taxa that may depend 

on freshwater aquatic invertebrate species may be indirectly affected is uncertain. 

As identified in previous assessments, methoxyfenozide is persistent and moderately mobile which 

combined with the fact that this compound acts through pathways which are common to a broad 

range of organisms that rely on ecdysone and undergo molting makes it plausible that 

methoxyfenozide may pose a greater long-term ecological risk than what is suggested by the 

screening-level assessment. 

Literature Cited 

Burns, Lawrence (2003). Exposure Analysis Modeling System (EXAMS): User Manual and System 

Documentation. Ecosystem Research Division, National Exposure Research Laboratory. U. S. 

Environmental Protection Agency, Athens, GA. 

California Department of Pesticide Regulation (CDPR) (2003). Methoxyfenozide. Public Report 2003-3. 

Tracking ID Numbers 195668 and 196546. 

Carsel, R.F., J.C. Imhoff, P.R. Humel, J.M. Cheplick, and A.S. Donigian, Jr. (2005). 

FAO, 2000. Food and Agriculture Organization of the United Nations. Pesticide Disposal Series 8. 

Assessing Soil Contamination: A Reference Manual. Appendix 2. Parameters of pesticides that influence 

processes in the soil. Editorial Group, FAO Information Division: Rome, 2000. 

http://www.fao.org/docrep/003/X2570E/X2570E00.htm. 

Goring, C.A. I.; Laskowki; D.A., Hamaker, J.H.; and Meikle, R.W. 1975. Principles of pesticide 

degradation in soil. pp. 135-172 in (Haque, R. and Freed, V.H. eds.) Environmental dynamics of pesticides. 

Plenum Press, NY. 

PRZM 3, A Model for Predicting Pesticide and Nitrogen Fate in the Crop Root and Unsaturated Zones: 

User’s Manual for Release 3.12.2. National Exposure Research Laboratory, Office of Research and 

Development, U. S. Environmental Protection Agency, Athens, GA. 
26

Shimizu, B., Y. Nakagawa, K. Hattori, K. Nishimura, N. Kurihara, and T. Ueno (1997). Molting hormonal 

and larvicidal activities of aliphatic acyl analogs of dibenzoylhydrazine insecticides. Steroids 62 (10): 638 

- 642. 

Trisyono, A., and G. M. Chippendale (1997). Effect of the non-steroidal ecdysone agonists, 

methoxyfenozide and tebufenozide, on the European corn borer (Lepidoptera; Pyralidae). J. Econ. 

Entomol., 90: 1486-1492. (ECOTOX No.: 64128). 

USEPA (2004). Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. 

U.S. Environmental Protection Agency, Endangered and Threatened Species Effects Determinations, 

Office of Prevention, Pesticides and Toxic Substances Office of Pesticide Programs, Washington, D.C. 

100 pgs. January 23. 

USEPA. 2009. Guidance for Selecting Input Parameters in Modeling the Environmental Fate and 

Transport of Pesticides. U.S. Environmental Protection Agency, Office Fate and Effects Division, Oct. 

22, 2009. Online at: http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm

USEPA. (2011). Review of Addendum to Site Selection Report with Recommended Alternate Sampling 

Sites for Lentic Water Bodies in California (MRID 47809904) (MRID: 478099-04). From C. Peck (EFED) 

and M. Echeverria (EFED) to C. Myers (RD) and R. Gebken (PRD). DP barcode 394308. October 12, 2011. 

 

USEPA (2013). Environmental Fate and Ecological Risk Assessment for Proposed Use of Methoxyfenozide on Herb 

Subgroup 19A (except chives), Dates, Sorghum, Fruiting Vegetable GFroup 8-10, Pome Fruit Group 11-10, Berry 

Subgroups 13-07 A, F & G, Tropical Tree Fruits AND Section 18 Emergency Exemption Petition for Use of 

Methoxyfenozide to Control Carob Moth on Dates. From Environmental Fate and Effects Division (EFED) to 

Registration Division (RD). DP Barcodes: 407284, 407808, 410683. June 13, 2013.

USEPA. 2013a. Methoxyfenozide: Review of Interim Report on Surface Water and Sediment Monitoring 

(MRID 49050001). Office of Chemical Safety and Pollution Prevention, Office of Pesticide Programs, 

From Environmental Fate and Effects Division (EFED) to Registration Division (RD); from C. Peck to M. 

Suarez. March 26, 2013. 

USEPA. 2013b. Registration Review: Preliminary Problem Formulation for Environmental Fate, 

Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure Assessments for 

Methoxyfenoxide. DP Barcode: D404482. Date: April 25, 2013. 

 
27

Appendix A: GENNEC Input/Output Files for Methoxyfenozide 

Pineapples (Ground) 

RUN No. 1 FOR Methoxyfenozide ON Pineapple * INPUT VALUES * 

-------------------------------------------------------------------- RATE 

(#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP ONE(MULT) 

INTERVAL Koc (PPM ) (%DRIFT) (FT) (IN) 

-------------------------------------------------------------------- 

.110(.437) 4 7 490.0 3.3 GRHIME (.8) 25.0 .0 

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

-------------------------------------------------------------------- 

METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED 

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND) 

-------------------------------------------------------------------- 

960.00 2 N/A .00- .00 ****** 1562.00 

GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001 

-------------------------------------------------------------------- 

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY 

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC 

-------------------------------------------------------------------- 

 13.46 13.42 13.20 12.73 12.39 

Pineapple (Aerial) 

RUN No. 2 FOR Methoxyfenozide ON Pineapple * INPUT VALUES * 

-------------------------------------------------------------------- 

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP 

 ONE(MULT) INTERVAL Koc (PPM ) (%DRIFT) (FT) (IN) 

-------------------------------------------------------------------- 

.110(.437) 4 7 490.0 3.3 AERL_C (1.9) 150.0 .0 

FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

-------------------------------------------------------------------- 

METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED 

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND) 

-------------------------------------------------------------------- 

 960.00 2 N/A .00- .00 ****** 1562.00 

GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001 

-------------------------------------------------------------------- 

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY 

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC 

-------------------------------------------------------------------- 

 13.22 13.18 12.97 12.50 12.17
28

SWCC Estimated Environmental Concentrations (ppb) for Methoxyfenozide and the USEPA 

Standard Pond. 

Table 1. PR Coffee scenario modeled with Puerto Rico Coffee weather file. 

Peak (1-in-10 yr) 35.1

4-day Avg (1-in-10 yr) 35.0

21-day Avg (1-in-10 yr) 34.7

60-day Avg (1-in-10 yr) 34.1

365-day Avg (1-in-10 yr) 31.7

Entire Simulation Mean 18.4

Table 2. PR Coffee scenario modeled with Oahu weather file (w22521) without modification to the 

Curve Number (85). 

Peak (1-in-10 yr) 41.0

4-day Avg (1-in-10 yr) 41.1

21-day Avg (1-in-10 yr) 40.9

60-day Avg (1-in-10 yr) 39.0

365-day Avg (1-in-10 yr) 35.0

Entire Simulation Mean 24.9

Table 3. PR Coffee scenario modeled with Oahu weather file (w22521) with Curve Number of 70. 

Peak (1-in-10 yr) 16.7

4-day Avg (1-in-10 yr) 16.8

21-day Avg (1-in-10 yr) 16.9

60-day Avg (1-in-10 yr) 16.1

365-day Avg (1-in-10 yr) 14.5

Entire Simulation Mean 9.64

Table 4. PR Coffee scenario modeled with Oahu weather file (w22521) with Curve Number of 90. 

Peak (1-in-10 yr) 63.8

4-day Avg (1-in-10 yr) 63.8

21-day Avg (1-in-10 yr) 63.2

60-day Avg (1-in-10 yr) 60.8

365-day Avg (1-in-10 yr) 55.0

Entire Simulation Mean 40.2
29

Table 5. PR Coffee scenario modeled with Maui weather file (w22516) without modification to the 

Curve Number (85). 

Peak (1-in-10 yr) 33.9

4-day Avg (1-in-10 yr) 33.9

21-day Avg (1-in-10 yr) 34.0

60-day Avg (1-in-10 yr) 31.3

365-day Avg (1-in-10 yr) 26.1

Entire Simulation Mean 20.8

Table 6. PR Coffee scenario modeled with Maui weather file (w22516) with Curve Number of 70. 

Peak (1-in-10 yr) 13.1

4-day Avg (1-in-10 yr) 13.1

21-day Avg (1-in-10 yr) 13.0

60-day Avg (1-in-10 yr) 12.3

365-day Avg (1-in-10 yr) 10.3

Entire Simulation Mean 7.85

Table 7. PR Coffee scenario modeled with Maui weather file (w22516) with Curve Number of 90. 

Peak (1-in-10 yr) 55.0

4-day Avg (1-in-10 yr) 54.9

21-day Avg (1-in-10 yr) 54.9

60-day Avg (1-in-10 yr) 50.2

365-day Avg (1-in-10 yr) 43.6

Entire Simulation Mean 34.5

Table 2. Summary of Model Inputs for Methoxyfenozide-Pineapple. 

Scenario PRcoffeeSTD 

Koc (ml/g) 490 

Water Half Life (days) @ 25 °C 1559 

Benthic Half Life (days) @ 25 °C 1962 

Photolysis Half Life (days) @ 40 

°Lat 

0 

Hydrolysis Half Life (days) 0 
30

Soil Half Life (days) @ 25 °C 960 

Foliar Half Life (days) 0 

Molecular Wt 368 

Vapor Pressure (torr) 2e-8 

Solubility (mg/l) 3.3 

 
31

APPENDIX B: Summary of the Available Toxicity Data for Methoxyfenozide. 

TABLE B.1. Summary of Submitted Toxicity Data for Methoxyfenozide and Aquatic 

Animals. 

Taxonomic 

Group 

Study 

Type 

Surrogate 

Species 

Toxicity Value 

(all units in 

terms of 

measured active 

ingredient) 

Acute Toxicity 

Classification Source 

(MRID) 

Study 

Classification 

Freshwater 

Fish 

96-Hour 

Acute 

Toxicity 

Rainbow trout 

Oncorhynchus 

mykiss

LC50 >4.2 mg/L 

(No mortality at 

the highest 

treatment level 

tested)

Moderately 

Toxic 441444-10 Acceptable 

Full Life 

Cycle 

Toxicity 

Fathead minnow 

Pimephales 

promelas

NOAEC = 0.53 

mg a.i./L 

LOAEC = 1.0 

(survival) 

N/A 446177-16 Acceptable 

Freshwater 

Invertebrates

48-hour 

Acute 

Toxicity 

Waterflea 

Daphnia magna

EC50 = 3.7 mg 

a.i./L 

Moderately 

Toxic 441444-11 Acceptable 

Estimate 

based on 

Acute-toChronic 

Ratio1

Midge 

Chironomus 

riparius

EC50 = 0.051 mg 

a.i./L 

(mortality) 

Very highly 

toxic N/A1 N/A 

Chronic 

Toxicity 

Waterflea 

Daphnia magna

NOAEC = 0.20 

mg a.i./L 

LOAEC = 0.39 

mg a.i./L 

(survival) 

N/A 446177-14 Acceptable 

Chronic 

Effects on 

Midge 

Larvae 

Midge 

Chironomus 

riparius

NOAEC=0.0063 

mg a.i./L 

LOAEC=0.013 

mg a.i./L 

(Delayed 

emergence and 

development) 

N/A 450328-01 Supplemental 

Estuarine/ 

Marine Fish 

96-Hour 

Acute 

Toxicity 

Sheepshead 

minnow 

Cyprinodon 

variegatus

96-hr LC50 >2.8 

mg a.i./L 

Moderately 

Toxic 441444-12 Acceptable 

Early Life 

Stage 

Toxicity 

Sheepshead 

minnow 

Cyprinodon 

variegatus

N/A N/A 446177-12 Currently under 

review in EFED 
32

Taxonomic 

Group 

Study 

Type 

Surrogate 

Species 

Toxicity Value 

(all units in 

terms of 

measured active 

ingredient) 

Acute Toxicity 

Classification Source 

(MRID) 

Study 

Classification 

Estuarine/ 

Marine 

Invertebrates 

96-Hour 

Shell 

Depositio

n 

Eastern oyster 

Crassostrea 

virginica

96-hr EC50 = 1.2 

mg a.i./L 

Moderately 

Toxic 441444-13 Acceptable 

Invertebra

te Life 

Cycle 

Toxicity 

Mysid 

Americamysis 

bahia (formerly

Mysidopsis 

bahia)

NOAEC = 0.025 

mg a.i./L 

LOAEC = 0.051 

mg a.i./L 

(Reduced 

growth/length) 

N/A 446177-15 Acceptable 

Non-Vascular 

Aquatic Plants 

5-Day 

Toxicity 

Test 

Freshwater alga 

Pseudokirchneri

ella subcapitata 

(formerly

Selenastrum 

capricornutum)

EC50 >3.4 mg 

a.i./L 

NOAEC= 3.4 mg 

a.i./L 

No effects at the 

highest treatment 

level tested 

N/A 446177-18 Acceptable 

1

 This endpoint is based on an acute to chronic ratio using acute and chronic data from daphnids and chronic data 

from midges. 

 
33

TABLE B.2. Summary of Available Toxicity Data for Methoxyfenozide and Terrestrial 

Animals.

Taxonomic 

Group 

Study 

Type 

Surrogate 

Species 

Toxicity Value 

(all units in 

terms of 

measured active 

ingredient) 

Acute Toxicity 

Classification Source 

(MRID) 

Study 

Classification 

Birds 

Acute 

Oral 

Toxicity 

Northern 

bobwhite quail

Colinus 

virginianus 

LD50 >2,250 mg 

a.i./kg-bw 

No effects at 

highest treatment 

level tested

Practically 

Non-Toxic 441444-06 Acceptable 

Subacute 

Dietary 

Toxicity 

Northern 

bobwhite quail

Colinus 

virginianus 

LC50 >5,870 

mg a.i./kg-diet 

No effects at 

highest treatment 

level tested 

Practically 

Non-Toxic 441444-07 Acceptable 

Avian 

Reproduct

ive 

Toxicity 

Northern 

bobwhite quail

Colinus 

virginianus 

NOAEC=520 mg 

a.i./kg-diet 

N/A 446177-11 Acceptable 

Mammals 

Acute oral 

Toxicity 

Rat 

Rattus norvegicus

LD50 >5,000 mg 

a.i./kg-bw 

Acute Toxicity 

Category 4 441444-15 Acceptable 

Chronic 

Dietary 

Toxicity 

Rat 

Rattus norvegicus

NOAEC = 8,000 

ppm diet 

(Survival) 

N/A 446177-31 Acceptable 

Terrestrial 

Invertebrates 

Acute 

Contact 

Toxicity 

Honey bee 

Apis mellifera 

LD50 >100 

μg/bee 

Practically 

Non-Toxic 441444-29 Acceptable 

Dietary 

Toxicity 

Honey bee 

Apis mellifera 

LC50 > 100 

μg/bee 

Practically 

Non-Toxic 446177-17 Supplemental 
34

Appendix C. 

T-REX Example Summary of Chronic Risk Quotient Calculations Based on Upper Bound 

Kenaga EECs for Pineapple for Birds and Mammals 

Upper Bound Kenaga, Acute Avian Dose‐Based  Risk Quotients

Size

Class

(grams)

Adjusted

LD50

EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods

/Seeds Arthropods Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

20 1620.97 98.87 0.06 45.31 0.03 55.61 0.03 6.18 0.00 38.72 0.02 1.37 0.00

100 2063.57 56.38 0.03 25.84 0.01 31.71 0.02 3.52 0.00 22.08 0.01 0.78 0.00

1000 2914.87 25.24 0.01 11.57 0.00 14.20 0.00 1.58 0.00 9.89 0.00 0.35 0.00

                         

Upper Bound Kenaga, Subacute Avian Dietary Based Risk Quotients       

LC50

EECs and RQs       

Short Grass Tall Grass Broadleaf

Plants Fruits/Pods/Seeds

EEC RQ EEC RQ EEC RQ EEC RQ   

5870 86.81 0.01 39.79 0.01 48.83 0.01 5.43 0.00      

Size class not used for dietary risk quotients            

                          

Upper Bound Kenaga, Chronic Avian Dietary Based Risk Quotients       

NOAEC

(ppm)

EECs and RQs       

Short Grass Tall Grass Broadleaf

Plants Fruits/Pods/Seeds

EEC RQ EEC RQ EEC RQ EEC RQ       

520 86.81 0.17 39.79 0.08 48.83 0.09 5.43 0.01      

Size class not used for dietary risk quotients          

 
35

                          

Upper Bound Kenaga, Acute  Mammalian Dose‐Based  Risk Quotients  

Size

Class

(gra

ms)

Adjus

ted

LD50

EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

15

1098

9.15 82.76

0.0

1 37.93 0.00 46.55 0.00 5.17 0.00 1.1495 0.0001

35

8891.

40 57.20

0.0

1 26.22 0.00 32.18 0.00 3.58 0.00 0.7945 9E‐05

1000

3845.

80 13.26

0.0

0 6.08 0.00 7.46 0.00 0.83 0.00 0.1842 5E‐05

                          

                          

                         

Upper Bound Kenaga, Chronic Mammalian Dietary Based Risk Quotients       

NOAEC

(ppm)

EECs and RQs       

Short Grass Tall Grass Broadleaf

Plants Fruits/Pods/Seeds/Large Insects

EEC RQ EEC RQ EEC RQ EEC RQ

8000 86.81 0.01

39.7

9 0.00 48.83 0.01 5.43 0.00

Size class not used for dietary risk quotients            

                         

Upper Bound Kenaga, Chronic Mammalian Dose‐Based Risk Quotients

Size

Class

(grams)

Adjusted

NOAEL

EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/

Seeds Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

15 879.13 82.76 0.09 37.93 0.04 46.55 0.05 5.17 0.01 1.15 0.00

35 711.31 57.20 0.08 26.22 0.04 32.18 0.05 3.58 0.01 0.79 0.00

1000 307.66 13.26 0.04 6.08 0.02 7.46 0.02 0.83 0.00 0.18 0.00

 
36

Appendix D. 

LOCATES Report